The primary objective of this research is to gain a better understanding of the mechanisms serving to regulate ventilation in health and disease. Mechanical loads to breathing (resistive and elastic) will be manipulated experimentally as a physiological probe to investigate the control system in humans (normal and asthmatics) and animal models. The ability of asthmatics to perceive mechanical loads to breathing will be determined and compared with normal subjects. The effect of individual differences in initial chemical and mechanical loading will be assessed and examined further by experimental manipulation of those variables. Programmable servo respirator devices will be developed to examine the effect of mechanical loading on the respiratory musculature and to determine the importance of rate of change of mechanical loading on load perception. In humans and animals, the effect of mechanical loads applied at different times on the breathing patterns (volumes and timing) will be analyzed in light of current theoretical models proposed to describe the interrelationships regulating depth and rate of breathing. Animal neurophysiological studies, employing microelectrode recording techniques, will investigate and characterize the behavior of the respiratory neurons of the brainstem in response to mechanical and chemical loading. Such recordings, combined with manipulations of the animal preparations (i.e., lesions, stimulation) will provide information regarding the origin and nature of the information responsible for eliciting change in respiratory neuron activity. Using iontophoretic techniques, in conjunction with glass microelectrodes, respiratory neurons responding to mechanical loading will be examined in terms of their neurotransmitter properties and their responsiveness to local H ion.